Implantable and Biodegradable Macroporous Iron Oxide Frameworks for Efficient Regeneration and Repair of Infracted Heart.

The construction, characterization and surgical application of a multilayered iron oxide-based macroporous composite framework were reported in this study. The framework consisted of a highly porous iron oxide core, a gelatin-based hydrogel intermediary layer and a matrigel outer cover, which conferred a multitude of desirable properties including excellent biocompatibility, improved mechanical strength and controlled biodegradability. The large pore sizes and high extent of pore interconnectivity of the framework stimulated robust neovascularization and resulted in substantially better cell viability and proliferation as a result of improved transport efficiency for oxygen and nutrients. In addition, rat models with myocardial infraction showed sustained heart tissue regeneration over the infract region and significant improvement of cardiac functions following the surgical implantation of the framework. These results demonstrated that the current framework might hold great potential for cardiac repair in patients with myocardial infraction.

Intelligent Drug Delivery System Based on Mesoporous Silica Nanoparticles Coated with an Ultra-pH-Sensitive Gatekeeper and Poly(ethylene glycol).

Mesoporous silica nanoparticles (MSNs) exhibit significant advantages for efficient drug/gene delivery but it is hard for simple MSNs to deliver the loaded drug to the target sites of disease. Considering that there are some well-known pH differences in the body, it is a useful strategy to modify the exterior surface of MSNs with stimuli-responsive gatekeepers to realize open-close transformation of their mesopores. In this work, multifunctional pH-sensitive MSNs were designed with mixed polymeric coatings, that is, poly(ethylene glycol) (PEG) as a dispersity-enhancer and poly(2-(pentamethyleneimino)ethyl methacrylate) (PPEMA) as an ultra-pH-sensitive gatekeeper. Enhanced dispersity, high drug loading capacity, long-circulation time, pH-triggered targeting, and better cellular uptake of the multifunctional MSNs make them potential candidates for pH-sensitive drug delivery such as tumor therapy.

Substrate-anchored and degradation-sensitive anti-inflammatory coatings for implant materials.

Implant materials need to be highly biocompatible to avoid inflammation in clinical practice. Although biodegradable polymeric implants can eliminate the need for a second surgical intervention to remove the implant materials, they may produce acidic degradation products in vivo and cause non-bacterial inflammation. Here we show the strategy of "substrate-anchored and degradation-sensitive coatings" for biodegradable implants. Using poly(lactic acid)/hydroxyapatite as an implant material model, we constructed a layer-by-layer coating using pH-sensitive star polymers and dendrimers loaded with an anti-inflammatory drug, which was immobilised through a hydroxyapatite-anchored layer. The multifunctional coating can effectively suppress the local inflammation caused by the degradation of implant materials for at least 8 weeks in vivo. Moreover, the substrate-anchored coating is able to modulate the degradation of the substrate in a more homogeneous manner. The "substrate-anchored and degradation-sensitive coating" strategy therefore exhibits potential for the design of various self-anti-inflammatory biodegradable implant materials.

Choline phosphate functionalized surface: protein-resistant but cell-adhesive zwitterionic surface potential for tissue engineering.

A choline phosphate (CP) modified surface is designed to resist protein adsorption due to its zwitterionic properties and simultaneously promote cell adhesion though its universal interaction with phosphate choline (PC) headgroups of the cell membrane. This work provides a new approach to obtain a cell-adhesive surface with a non-biofouling 'background', which has a potential for tissue engineering.

Controlled co-delivery nanocarriers based on mixed micelles formed from cyclodextrin-conjugated and cross-linked copolymers.

The combination of multiple drugs within a single nanocarrier can provide significant advantages for disease therapy and it is desirable to introduce a second drug based on host-guest interaction in these co-delivery systems. In this study, a core-stabilized mixed micellar system consisting of ß-cyclodextrin-conjugated poly(lactic acid)-b-poly(ethylene glycol) (ß-CD-PLA-mPEG) and DL-Thioctic acid (TA) terminated PLA-mPEG (TA-PLA-mPEG) was developed for the co-delivery of DOX and fluorescein isothiocyanate labeled adamantane (FA). DOX can be loaded within the hydrophobic segment of PLA and FA may form stable complexation with ß-CD in the core. The mixed micelles (MM) are based on well-accepted medical materials and can be easily cross-linked by adding 1,4-dithio-D,L-threitol (DTT), which can enhance the stability of the system. Drug-loaded MM system was characterized in terms of particle size, morphology, drug loading and in vitro release profile. Cytotoxicity test showed that blank MM alone showed negligible cytotoxicity whereas the drug-loaded MM remained relatively high cytotoxicity for HeLa cancer cells. Confocal laser scanning microscopy (CLSM) demonstrated that the MM could efficiently deliver and release DOX and FA in the same tumor cells to effectively improve drugs' bioavailability. These results suggested that the core-stabilized MM are highly promising for intracellular co-delivery of multiple drugs.

Phosphorylated dendronized poly(amido amine)s as protein analogues for directing hydroxylapatite biomineralization.

Dendronized poly(amido amine)s (DPs) bearing tri-phosphate or bis-phosphonate peripheral groups are synthesized. These worm-like DPs can template the formation of BMSCs adhesive hydroxylapatite (HA) on the nano-scale, or self-assemble into mineral-collecting microfibers on the micro-scale, exhibiting similar functions of non-collagenous proteins (NCPs) in the natural biomineralization process of HA.